Lee M S
Department of Chemical Carcinogenesis, Michigan Cancer Foundation, Detroit 48201.
Chem Res Toxicol. 1992 Nov-Dec;5(6):791-6. doi: 10.1021/tx00030a010.
The present study investigated the oxidative metabolism of 2-naphthyl isothiocyanate catalyzed by rat liver microsomes. Incubation of 2-naphthyl isothiocyanate, microsomes, and NADPH yielded either N,N'-di-2-naphthylurea or, on inclusion of 2-aminofluorene in the incubations, N-2-naphthyl-N'-2-fluorenylurea. These ureas were formed by the production of 2-naphthyl isocyanate, which reacted with its hydrolysis product, 2-aminonaphthalene, to yield the symmetrical urea or, with 2-aminofluorene, to form the mixed urea. Formation of N,N'-di-2-naphthylthiourea was also observed, since 2-aminonaphthalene reacted with the substrate. Urea formation was dependent on microsomes, NADPH, and O2. Use of microsomes from rats previously treated with Aroclor increased urea formation > or = 10-fold. The enzyme activity was inhibited by alpha-naphthoflavone, flavone, or CO and slightly inhibited by metyrapone, 7-ethoxycoumarin, or SKF-525A. It was not inhibited by methimazole or paraoxon. These data are consistent with a cytochrome P-450-dependent, oxidative desulfuration of the isothiocyanate to yield an isocyanate.
本研究调查了大鼠肝脏微粒体催化的异硫氰酸2-萘酯的氧化代谢。将异硫氰酸2-萘酯、微粒体和NADPH一起温育，会产生N,N'-二-2-萘基脲；或者在温育体系中加入2-氨基芴时，会产生N-2-萘基-N'-2-芴基脲。这些脲是由异氰酸2-萘酯生成的，它与其水解产物2-氨基萘反应生成对称脲，或者与2-氨基芴反应生成混合脲。由于2-氨基萘与底物发生反应，因此也观察到了N,N'-二-2-萘基硫脲的形成。脲的形成依赖于微粒体、NADPH和氧气。使用先前用多氯联苯处理过的大鼠的微粒体，脲的形成增加了≥10倍。该酶活性受到α-萘黄酮、黄酮或一氧化碳的抑制，受到甲吡酮、7-乙氧基香豆素或SKF-525A的轻微抑制。它不受甲巯咪唑或对氧磷的抑制。这些数据与细胞色素P-450依赖性的异硫氰酸酯氧化脱硫生成异氰酸酯是一致的。
